Laboratory of Experimental Carcinogenesis, National Cancer Institute, Building 37, Room 4140, 37 Convent Dr., MSC 4262, Bethesda, MD, 20892-4262, USA,
Mol Diagn Ther. 2014 Jun;18(3):293-302. doi: 10.1007/s40291-014-0086-3.
While significant progress continues to be made in the early detection and therapeutic management of primary tumors, the incidence of metastatic disease remains the major cause of mortality. Accordingly, the development of novel effective therapies that can ameliorate dissemination and secondary tumor growth are a clinical priority. The identification of genetic and functional alterations in cancer cells that affect factors implicated in the metastatic process is critical for designing preventive and therapeutic strategies. Evidence implicating the protein deleted in liver cancer-1 (DLC1), a Rho GTPase activator, in metastasis has accumulated to a point where DLC1 may be considered as a metastasis suppressor gene. This review presents evidence supporting an anti-metastatic role for DLC1 in several human cancers and discusses the mechanisms contributing to its inhibitory effects. In addition, promising opportunities for therapeutic interventions based on DLC1 function and downstream pathways involved in the metastatic process are considered.
虽然在原发性肿瘤的早期检测和治疗管理方面继续取得重大进展,但转移性疾病的发病率仍是导致死亡的主要原因。因此,开发能够改善播散和继发肿瘤生长的新型有效治疗方法是临床重点。鉴定影响转移过程中相关因素的癌细胞中的遗传和功能改变对于设计预防和治疗策略至关重要。有证据表明,肝癌缺失蛋白 1(DLC1),一种 Rho GTPase 激活剂,与转移有关,以至于 DLC1 可以被认为是一种转移抑制基因。本综述提供了支持 DLC1 在几种人类癌症中具有抗转移作用的证据,并讨论了促成其抑制作用的机制。此外,还考虑了基于 DLC1 功能和转移过程中涉及的下游途径的治疗干预的有希望的机会。